PROJECT SUMMARY/ABSTRACT This K23 career development award will establish the critical launching step of Dr. Xiao's career as a clinician- scientist focusing on early childhood caries and severe early childhood caries (ECC/S-ECC) research. The grant will support her development of key expertise in 4 areas: 1) Refine skills in epidemiological research in cariology, including caries risk assessment and diagnostic systems; 2) Enhance skills in cutting-edge applied microbiology for translational dental research; 3) Design and conduct clinical studies and clinical trials; and 4) Improve skills in scientific communications. To achieve these goals, Dr. Xiao has assembled a multidisciplinary mentoring team with expertise in dental translational/clinical research (primary mentor, Dr. Kopycka), microbiology-biofilm/cariology (co-primary mentor, Dr. Koo), caries epidemiology (secondary mentor, Dr. Billings), epidemiology (secondary mentor, Dr. van Wijngaarden), and biostatistics (secondary mentor, Dr. Feng). Dr. Xiao is also strongly supported by an advisory committee with Dr. Mendoza (family medicine), Dr. Quivey (oral microbiology), Dr. Gill (oral genomics), Dr. Rustchenko (Candida albicans chromosome research) and Dr. Baldwin (scientific writing). ECC is the most common chronic disease of childhood and disproportionately afflicts socioeconomically disadvantaged children worldwide. Emerging evidence on the role of Candida species in ECC/S-ECC has spotlighted potential approaches to early prediction and subsequent prevention of this disease from a fungal perspective. However, only cross-sectional human studies have been performed thus far. Without prospective cohort studies through the age of S-ECC onset and further clarification of microbiological contributions, it remains unclear how Candida detection is linked with the disease process and whether this fungal organism could be a reliable marker for risk of onset and progression of S-ECC. The immediate goal of this K23 proposal is to build upon and expand the cohort/framework used in Dr. Xiao's KL2 by conducting a 2-year prospective cohort study to investigate the association between oral C. albicans carriage and the onset of S-ECC, and to explore the underlying microbiological mechanisms. The overarching hypotheses are that oral C. albicans could be used as novel biological marker for S-ECC in combination with the current bacterial risk factors, and that the presence of Candida enhances S. mutans colonization and disrupts the oral microbiota in early infancy. To test these hypotheses, Dr. Xiao will study the association between C. albicans oral colonization in infants at high risk for S-ECC and the onset/severity of S-ECC (AIM 1); Analyze the association between oral carriage of C. albicans and S. mutans in infants (birth to 2 years) (AIM 2); Evaluate the influence of oral C. albicans on oral microbiota in early infancy (AIM 3). In summary, this K23 award will provide Dr. Xiao with training, experience and research accomplishments that will lay the foundation for future NIH applications. Results from this cohort study and subsequent studies may lead to new pathways for developing novel caries-predictive and -preventive strategies from a fungal perspective.